Search Results (558)

Background: Prostate cancer (PCa) trends have evolved due to changing screening practices. This study assessed long-term trends in PCa incidence and survival according to Gleason score (GS) in Friuli Venezia Giulia, northeastern Italy. Methods: A population-based study was conducted, encompassing 21,571 PCa cases from the regional Cancer Registry, diagnosed between 2000 and 2020. Age-standardized incidence rates and 5-year overall (OS) and net survival (NS) were assessed by GS (2–6, 7, 8–10) and age group (<65, 65–74, ≥75). Trends were analyzed using Joinpoint regression. Results: PCa incidence increased from 2000 to 2007 (Annual Percent Change, APC = +1.8%), then declined sharply until 2010 (APC = −7.6%) and remained stable thereafter. Incidence of low-grade cancers (GS 2–6) decreased across all age groups, especially in men aged ≥ 75 years (APC = −8.1%). The incidence of GS 7 rose until 2007 and then stabilized. High-grade cancers (GS 8–10) showed a stable incidence, but their proportion increased from 20% to 29%, mainly in older men. Survival improved across all GS groups. For GS 2–6, OS increased from 81.4% to 88.2%; for GS 7, from 78.1% to 88.1%. GS 8–10 had smaller gains, but NS reached 82% in recent years. Among men aged ≥ 75 years, OS for GS 7 rose from 51.9% to 78.1%, and for GS 8–10, from 43.9% to 54.4%. NS remained high for GS ≤ 7. Conclusions: While overall outcomes improved, the increasing proportion of high-grade PCa, despite a stable incidence, raises concerns, particularly in older men, and calls for tailored clinical strategies. Full article

Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8–10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed. Results: Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, p = 0.0139) and FFDM (93% vs. 72%, p = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 0.05). Conclusions: TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials. Full article

Background/Objectives: Prostate cancer (PCa) is diagnosed at an earlier median age, more advanced stage, and has worse clinical outcomes in African American (AA) men compared to European Americans (EA). Methods: To investigate the role of aberrant DNA methylation in tumor-adjacent stroma (TAS), methyl binding domain sequencing (MBD-seq) was performed on AA (n = 17) and EA (n = 15) PCa patients. This was independently confirmed using the long interspersed nuclear element-1 (LINE-1) assay. Pathway analysis was performed on statistically significantly differentially methylated genes for AA and EA TAS. DNA methylation profiles of primary cultured AA and EA carcinoma-associated fibroblasts (CAFs) were compared with AA and EA TAS. AA and EA CAFs were treated with demethylating agent 5-Azacytidine (5-AzaC). Results: AA TAS exhibited higher global DNA methylation than EA TAS (p-value < 0.001). Of the 3268 differentially methylated regions identified (DMRs, p-value < 0.05), 85% (2787 DMRs) showed increased DNA methylation in AA TAS, comprising 1648 genes, of which 1379 were protein-coding genes. Based on DNA methylation levels, two AA subgroups were identified. Notably, AA patients with higher DNA methylation were predominantly those with higher Gleason scores. Pathway analysis linked methylated genes in AA TAS to several key signaling pathways (p-value < 0.05), including immune response (e.g., IL-1, IL-15, IL-7, IL-8, IL-3, and chemokine), Wnt/β-catenin, androgen, PTEN, p53, TGF-β, and circadian clock regulation. A total of 168 concordantly methylated genes were identified, with 109 genes (65%) showing increased methylation in AA CAFs and TAS (p-value < 0.05). Treatment with 5-AzaC significantly reduced DNA methylation of concordant genes in AA CAFs (p-value < 0.001). Conclusions: These findings suggest a distinct stromal methylome in AA, providing a foundation for integrating demethylating agents into standard therapies. This approach targets the tumor microenvironment, potentially addressing PCa disparities in AA men. Full article

This paper assesses the complexity and diversity of vegetation in grassy strips with spontaneous plants between tree rows in three fruit orchards (plum, cherry, apple) in Dolj County, Romania, using structural and biodiversity indices. It addresses the lack of data on spontaneous vegetation in Romanian orchards, supporting improved plantation management and native biodiversity conservation. The study found that grassy strips supported high wild herbaceous diversity and a complex, heterogeneous ecological structure, with the apple orchard showing the highest biodiversity. Species diversity, evaluated through species richness, evenness, and diversity indices (Shannon, Simpson, Menhinick, Gleason, etc.), showed species richness ranging from 30 species in the cherry orchard to 40 in the apple orchard. Several species, including Capsella bursa-pastoris, Geranium pusillum, Poa pratensis, Veronica hederifolia, Lolium perenne, and Convolvulus arvensis, were present in 100% of samples, making them constant species from a phytosociological perspective. Their presence indicates relatively stable plant communities in each orchard. From a phytocoenological view, an ecological plant community is defined not only by species composition but also by constancy and co-occurrence in sampling units. Dominance remained low in all orchards, indicating no single plant dominated, while evenness showed a uniform distribution of species. Full article

Gleason score (GS) is one of the best predictors of prostate cancer (PCa) aggressiveness; however, its biological features need to be elucidated. This study aimed to explore the biological characteristics of localized/locally advanced PCa stratified using in silico GS analysis. Biological features were analyzed using gene set variation analysis and the xCell algorithm with mRNA expression in two independent public databases: The Cancer Genome Atlas (TCGA) (n = 493; radical prostatectomy cohort) and GSE116918 (n = 248; radiation therapy cohort). GS levels were positively correlated with the activity levels of cell proliferation-related gene sets, including E2F targets, the G2M checkpoint, the mitotic spindle, and MYC targets v1 and v2 in both cohorts. Furthermore, GS levels were positively associated with the activity levels of immune-related gene sets and infiltrating fractions of immune cells, including CD4+ memory T cells, dendritic cells, M1 macrophages, and Th2 cells, in both cohorts. Notably, GS levels were positively associated with the score levels of homologous recombination defects, intratumor heterogeneity, fraction genome alteration, neoantigens, and mutation rates in the TCGA cohort. In conclusion, PCa with high GS levels was associated with cancer cell proliferation, immune cell infiltration, and high mutation rates, which may reflect worse clinical outcomes. Full article

Urinary extracellular vesicles (U-EVs) are gaining increasing interest as non-invasive liquid biopsy tools for clinical use. Prostate cancer (PCa) is amongst the highest cancer-related cause of death in men, and therefore, the identification of non-invasive robust biomarkers is of high importance. This study assessed U-EV profiles from individuals affected by PCa at Gleason scores 6–9, compared with healthy controls. U-EVs were characterised and assessed for proteomic cargo content by LC-MS/MS analysis. The U-EV proteomes were compared for enrichment of gene ontology (GO), KEGG, and Reactome pathways, as well as disease–gene associations. U-EVs ranged in size from 50 to 350 nm, with the majority falling within the 100–200 nm size range for all groups. U-EV protein cargoes from the PCa groups differed significantly from healthy controls, with 16 protein hits unique to the GS 6–7 and 88 hits to the GS 8–9 U-EVs. Pathway analysis showed increased enrichment in the PCa U-EVs of biological process GO (5 and 37 unique to GS 6–7 and GS 8–9, respectively), molecular function GO (3 and 6 unique to GS 6–7 and GS 8–9, respectively), and cellular component GO (10 and 22 unique to GS 6–7 and GS 8–9, respectively) pathways. A similar increase was seen for KEGG pathways (11 unique to GS 8–9) and Reactome pathways (102 unique to GS 8–9). Enrichment of disease–gene associations was also increased in the PCa U-EVs, with highest differences for the GS 8–9 U-EVs (26 unique terms). The pathway enrichment in the PCa U-EVs was related to several key inflammatory, cell differentiation, cell adhesion, oestrogen signalling, and infection pathways. Unique GO and KEGG pathways enriched for the GS 8–9 U-EVs were associated with cell–cell communication, immune and stress responses, apoptosis, peptidase activity, antioxidant activity, platelet aggregation, mitosis, proteasome, mRNA stability oxytocin signalling, cardiomyopathy, and several neurodegenerative diseases. Our findings highlight U-EVs as biomarkers to inform disease pathways in prostate cancer patients and offer a non-invasive biomarker tool for clinical use. Full article

The present study analyzed the vegetation diversity in three forests located in southern Romania and assessed their degree of similarity. Data were collected using frame quadrat sampling and species taxonomic identification. The methodology included the calculation of ecological indices (Shannon–Wiener, equitability, maximum entropy, Menhinick, Margalef, McIntosh, Gleason, and Simpson) and statistical analysis using ANOVA and Duncan tests (p < 0.05). Similarity between forests was evaluated using the Jaccard and Dice/Sørensen coefficients. The results showed that biodiversity increases with area size, and the forest ecosystem in Vlădila exhibited the highest number of woody and herbaceous species. Although the forest ecosystem in Studinița had the greatest floristic diversity, according to the Shannon–Wiener index, it also showed higher equitability (0.911 compared to 0.673 in Vlădila) due to a more uniform species distribution. The forest ecosystem in Studinița acted as an intermediate zone between those in Grădinile and Vlădila. Variations in diversity among the three areas reflect ecological differences influenced by location-specific factors such as soil type, climatic conditions, and human interventions. This suggests that ecological conditions and the physical characteristics of forests significantly impact the number and types of species that can coexist within an ecosystem. Full article

Purpose: Despite increasing rates of prostate cancer among men, prostate cancer risk assessments continue to rely on invasive laboratory tests like prostate-specific antigen and Gleason score tests. This study aimed to develop a noninvasive, data-driven risk model for patients to evaluate themselves before deciding whether to visit a hospital. Materials and Methods: To train the model, data from the National Health Insurance Sharing Service cohort datasets, comprising 347,575 individuals, including 1928 with malignant neoplasms of the prostate, 5 with malignant neoplasms of the penis, 18 with malignant neoplasms of the testis, and 14 with malignant neoplasms of the epididymis, were used. The risk model harnessed easily accessible inputs, such as history of treatment for diseases including stroke, heart disease, and cancer; height; weight; exercise days per week; and duration of smoking. An additional 286,727 public datasets were obtained from the National Health Insurance Sharing Service, which included 434 (0.15%) prostate cancer incidences. Results: The risk calculator was built based on Cox proportional hazards regression, and I validated the model by calibration using predictions and observations. The concordance index was 0.573. Additional calibration of the risk calculator was performed to ensure confidence in accuracy verification. Ultimately, the actual proof showed a sensitivity of 60 (60.5) for identifying a high-risk population. Conclusions: The feasibility of the model to evaluate prostate cancer risk without invasive tests was demonstrated using a public dataset. As a tool for individuals to use before hospital visits, this model could improve public health and reduce social expenses for medical treatment. Full article

Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite base repeats in cells. Assessing the frequency of MSI is essential, as it may identify candidates for immune checkpoint inhibitors, which have shown promising outcomes. This study focuses on evaluating the MSI frequency in Mexican PCa patients and exploring its potential relationship with tumor aggressiveness. Methods: In this study, 116 formalin-fixed paraffin-embedded tumoral tissue biopsies from Mexican patients with PCa were collected from Hospital Civil de Culiacán and Pathology and Nephropathology, Diagnosis and Research Center, in the period from 2021 to 2024. The Gleason score was assessed, and the MSI was performed by multiplex PCR with a panel of five markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26). High microsatellite instability (MSI-H) was defined as two or more unstable markers, low microsatellite instability (MSI-L) as an unstable marker, and microsatellite stability (MSS) as no unstable marker. Results: We found 19.83% (23/116) MSI PCa patients, of which 21.74% (5/23) were MSI-H, and 78.26% (18/23) were MSI-L. We found a major distribution of MSI-positive cases (50% (11/22)) in Gleason score 9 patients, corresponding to prognostic group 5. In addition, we found most of the instability in the BAT-26 marker in MSI PCa patients (60.87% (14/23)). Conclusions: This study is the first to evaluate the frequency of MSI in PCa within the Mexican population. Among the Mexican patients with MSI-positive PCa, there was a predominant Gleason score 9 and a majority instability of the BAT-26 marker. Full article

Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve patient prognosis. This study aims to investigate the impact of the presence and severity of PVFs on overall survival in patients with nmPC undergoing androgen deprivation therapy (ADT). Methods: A total of 275 men (median age: 73 years) with nmPC who underwent ADT were studied retrospectively. The median observation period was 55 months. Variables included age, body mass index, T classification, N classification, Gleason score, and pretreatment serum prostate-specific antigen levels. PVF was diagnosed from the sagittal computed tomography images of Th1 to L5 before initiating ADT, and the severity was determined by the number of PVFs and the Semiquantitative (SQ) method. Hazard ratios and 95% confidence intervals for overall survival were calculated using the Cox proportional hazards model. Results: During the observation period, 30 patients died from all causes. Multivariate Cox regression analysis identified multiple PVFs and high-grade PVFs, as determined by the SQ method, as significant predictors of overall survival. The analysis utilized two adjustment models: one adjusted for age only and the other adjusted for age, Gleason score, and clinical T stage. Conclusions: Multiple PVFs and high-grade PVF determined by the SQ method prior to ADT initiation were associated with higher all-cause mortality in nmPC patients treated with ADT. Full article

Background: Irreversible electroporation (IRE) is a novel ablative treatment modality for localized prostate cancer and aims at achieving oncological control while minimizing the related side effects. We present the functional and oncological outcomes of focal IRE ablation versus hemi-ablation from a single-center patient series. Methods: Men with histologically confirmed low–intermediate risk prostate cancer received focal IRE ablation or hemi-ablation. All the patients were recommended an MRI-targeted fusion biopsy plus systematic biopsy at 1 year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Results: In total, 106 patients were recruited in this study. The median follow-up time was 24 months (IQR 15–36). Overall, 94 patients underwent repeat prostate biopsy at 12 months after IRE. Persistent tumor was detected in 72.2% in the focal ablation group and in 31% in the hemi-ablation group (p < 0.001). Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 25% in the focal ablation group and in 8.6% in the hemi-ablation group (p = 0.003). There was no significant difference between the two groups in terms of IPSS and IIEF at each follow-up time point. Conclusion: For men with localized low–intermediate risk prostate cancer, hemi-IRE ablation treatment displayed better oncological control than focal ablation without compromising on functional or sexual outcomes. Full article

A relatively new GelSight Max measurement instrument was applied to the microtopographies of experimental hardened clay surfaces, both with and without fingerprint (dermatoglyph) impressions, and the surface of an archaeological pottery handle fragment with a preserved fingerprint (paleodermatoglyph). The experimental clay surfaces were documented in order to determine the instrument’s ability to capture these surfaces in three-dimensions by imprinting them onto an elastomeric tactile membrane. Fingerprints on the experimental hardened clay and the archaeological pottery fragment were mathematically documented to test this instrument’s ability to capture these impressions. The surface texture measurements of the hardened clay and the pottery fragment were mathematically compared using conventional topographic characterization parameters (height and hybrid), fractal dimensions (Das) with associated coefficients of determination (R²), and multiscalar geometric characterization parameters, particularly relative area (Srel), area-scale complexity (Asfc), relative length (RL), and length-scale complexity (Lsfc). The surfaces of the experimental hardened clay with and without fingerprints and the archaeological pottery handle fragment with a fingerprint can be discriminated using some conventional height parameters, as well as some multiscale geometric topographic characterization parameters. Specifically, relative area (Srel), area-scale complexity (Asfc), relative length (RL), and length-scale complexity (Lsfc) could all discriminate between the hardened clay block with and without fingerprints and the fingerprint on the archaeological pottery handle fragment at different scales of measurement. Mean square ratios (MSRs) above 90% and 95% confidence levels indicated that the discrimination of these multiscale geometric characterizations was significant. In sum, the GelSight Max has the potential to be a valuable instrument for archaeologists studying pottery and fingerprints. Full article

In response to systemic inequities in mathematics education, we developed and evaluated a five-year, multi-phase curriculum model to cultivate effective secondary mathematics teacher leaders. Supported by NSF Noyce Master Teacher Fellowships, the APLUS in MATH (APLUS in Math: Alabama Practitioner Leaders for Underserved Schools in Mathematics) program engaged 22 inservice teachers through graduate coursework, National Board Certification preparation, and leadership project development. Using a mixed-methods design, we analyzed data from classroom observations (MCOP²), National Board Certification assessments, course performance ratings, and teacher leadership project proposals. Results indicate significant improvements in instructional practices, content knowledge, and leadership readiness. Findings underscore the importance for sustained, structured professional development to prepare teachers as instructional experts and change agents in high-need educational contexts. Full article

Introduction: The treatment efficacy of prostate cancer (PCa) radiotherapy (RT) can be inadvertently affected by the concurrent usage of non-oncologic medications. Many studies have associated the intake of several non-oncologic drugs with cancer specific outcomes. In this study, we report the impact of daily non-oncologic medications including aspirin, metformin, and statins on time to progression for patients with high-risk PCa. Methods: Patients with high- and very high risk PCa (NCCN definition of Gleason score ≥ 8, prostate-specific antigen (PSA) ≥ 20, or ≥cT3a) who received definitive RT at two institutions were included in this analysis. Progression was defined as either biochemical (PSA > nadir + 2 ng/mL), locoregional (prostate or lymph nodes, biopsy-proven), or development of distant metastases. Progression-free survival (PFS) was defined as the time elapsed from the start of RT to progression or last follow-up. Cox proportional hazards models evaluated the associations between non-oncologic medications and PFS. Results: There were 237 patients eligible for this analysis, of which 47 (19.8%) and 178 (75.1%) had at least clinical T3 disease or at least Gleason 8 disease, respectively. During RT, 82 (34.6%), 88 (37.1%), and 29 (12.2%) patients were taking aspirin, statin, or metformin, respectively. Overall, 54 patients (22.8%) experienced disease progression. Neither aspirin nor statin usage had a significant association with PFS. Patients prescribed metformin displayed worse PFS compared to patients not taking metformin (aHR: 2.46, 95% CI: 1.06–5.72). Conclusions: Aspirin and statin usage was not associated with likelihood of progression in this large cohort of patients with high-/very high risk PCa. Metformin use was associated with poorer PFS, albeit with a small event rate due to fewer patients taking metformin. Further studies are needed to clarify the impact of common non-oncologic medication use on outcomes for patients with high-risk PCa. Full article

Background/Objectives: The aim of this study was to demonstrate the importance of ⁶⁸Gallium (⁶⁸Ga)–prostate specific membrane antigen (PSMA)–positron emissions tomography (PET)/computed tomography (CT)(PET/CT) in prostate cancer patients for therapy management with individual analyses regarding the Gleason score, prostate specific antigen (PSA) value, and the risk groups defined by D’Amico. Methods: We retrospectively analyzed 562 ⁶⁸Ga-PSMA-11-PET/CT examinations performed from January 2015 to March 2023 at University Hospital Marburg. We assessed treatment changes post ⁶⁸Ga-PSMA-11-PET/CT and categorized the cases based on PSA values, Gleason scores, and D’Amico risk groups. Results: In 415/562 (73.8%) of ⁶⁸Ga-PSMA-11-PET/CT examinations, a modification in the therapy concept was recorded. Patients categorized as high risk or patients with Gleason scores of 7 through 10 or with PSA levels above 0.5 ng/mL (particularly within the ranges of 1.01–2 ng/mL, 3.01–5 ng/mL, and values exceeding 10 ng/mL) demonstrated a statistically significant association with treatment change. While no evidence of the disease was found most frequently in 38% of cases in the “Therapy continued without explicit reference” group, in the group with the adapted therapy, there was a considerable higher proportion of local tumors (19.2%) compared to the other groups (4.4% and 1.4%). Conclusions: Our results show the high impact of ⁶⁸Ga-PSMA-PET/CT for patients with prostate cancer regarding therapy management planning, which is even more important for some patient groups. Full article